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FältnamnIndikatorerMetadata
00005953naa a2200613 4500
001oai:gup.ub.gu.se/268567
003SwePub
008240528s2018 | |||||||||||000 ||eng|
0247 a https://gup.ub.gu.se/publication/2685672 URI
0247 a https://doi.org/10.1093/humrep/dey0262 DOI
040 a (SwePub)gu
041 a eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Heinosalo, T.4 aut
2451 0a Secreted frizzled-related protein 2 (SFRP2) expression promotes lesion proliferation via canonical WNT signaling and indicates lesion borders in extraovarian endometriosis
264 c 2018-02-15
264 1b Oxford University Press (OUP),c 2018
520 a STUDY QUESTION: What is the role of SFRP2 in endometriosis? SUMMARY ANSWER: SFRP2 acts as a canonical WNT/CTNNBI signaling agonist in endometriosis, regulating endometriosis lesion growth and indicating endometriosis lesion borders together with CTNNBI (also known as beta catenin). WHAT IS KNOWN ALREADY: Endometriosis is a common, chronic disease that affects women of reproductive age, causing pain and infertility, and has significant economic impact on national health systems. Despite extensive research, the pathogenesis of endometriosis is poorly understood, and targeted medical treatments are lacking. WNT signaling is dysregulated in various human diseases, but its role in extraovarian endometriosis has not been fully elucidated. STUDY DESIGN, SIZE, DURATION: We evaluated the significance of WNT signaling, and especially secreted frizzled-related protein 2 (SFRP2), in extraovarian endometriosis, including peritoneal and deep lesions. The study design was based on a cohort of clinical samples collected by laparoscopy or curettage and questionnaire data from healthy controls and endometriosis patients. PARTICIPANTS/MATERIALS, SETTING, METHODS: Global gene expression analysis in human endometrium ( n = 104) and endometriosis (n = 177) specimens from 47 healthy controls and 103 endometriosis patients was followed by bioinformatics and supportive qPCR analyses. Immunohistochemistry, Western blotting, primary cell culture and siRNA knockdown approaches were used to validate the findings. MAIN RESULTS AND THE ROLE OF CHANCE: Among the 220 WNT signaling and CTNNBI target genes analysed, 184 genes showed differential expression in extraovarian endometriosis (P < 0.05) compared with endometrium tissue, including SFRP2 and CTNNI. Menstrual cycle-dependent regulation of WNT genes observed in the endometrium was lost in endometriosis lesions, as shown by hierarchical clustering. Immunohistochemical analysis indicated that SFRP2 and CTNNBI are novel endometriosis lesion border markers, complementing immunostaining for the known marker CD10 (also known as MME). SFRP2 and CTNNBI localized similarly in both the epithelium and stroma of extraovarian endometriosis tissue, and interestingly, both also indicated an additional distant lesion border, suggesting that WNT signaling is altered in the endometriosis stroma beyond the primary border indicated by the known marker CD10. SFRP2 expression was positively associated with pain symptoms experienced by patients (P < 0.05), and functional loss of SFRP2 in extraovarian endometriosis primary cell cultures resulted in decreased cell proliferation (P < 0.05) associated with reduced CTNNBI protein expression (P = 0.05). LIMITATIONS REASONS FOR CAUTION: SFRP2 and CTNNBI improved extraovarian endometriosis lesion border detection in a relatively small cohort (n = 20), although larger studies with different endometriosis subtypes in variable cycle phases and under hormonal medication are required. WIDER IMPLICATIONS OF THE FINDINGS: The highly expressed SFRP2 and CTNNBI improve endometriosis lesion border detection, which can have clinical implications for better visualization of endometriosis lesions over CD10. Furthermore, SFRP2 acts as a canonical WNT/CTNNBI signaling agonist in endometriosis and positively regulates endometriosis lesion growth, suggesting that the WNT pathway may be an important therapeutic target for endometriosis.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Reproduktionsmedicin och gynekologi0 (SwePub)302202 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Obstetrics, Gynaecology and Reproductive Medicine0 (SwePub)302202 hsv//eng
653 a endometriosis
653 a extraovarian endometriosis
653 a SFRP2
653 a canonical WNT signaling
653 a CD10
653 a beta-catenin
653 a e-cadherin
653 a pathogenesis
653 a pathway
653 a cancer
653 a growth
653 a cells
653 a women
653 a progesterone
653 a metabolism
7001 a Gabriel, M.4 aut
7001 a Kallio, L.4 aut
7001 a Adhikari, P.4 aut
7001 a Huhtinen, K.4 aut
7001 a Laajala, T. D.4 aut
7001 a Kaikkonen, E.4 aut
7001 a Mehmood, A.4 aut
7001 a Suvitie, P.4 aut
7001 a Kujari, H.4 aut
7001 a Aittokallio, T.4 aut
7001 a Perheentupa, A.4 aut
7001 a Poutanen, Mattiu Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition4 aut0 (Swepub:gu)xpouma
7102 a Göteborgs universitetb Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition4 org
7730 t Human Reproductiond : Oxford University Press (OUP)g 33:5, s. 817-831q 33:5<817-831x 0268-1161x 1460-2350
8564 u https://academic.oup.com/humrep/article-pdf/33/5/817/24756684/dey026.pdf
8564 8u https://gup.ub.gu.se/publication/268567
8564 8u https://doi.org/10.1093/humrep/dey026

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